DISEASE AREA COORDINATORS

Prof. Dr. Andreas Günther (UGMLC), PD Dr. Anne Hilgendorff (CPC-M)

(Administr. Coordinator: Dr. Antje Brand (CPC-M))

CONTRIBUTING PARTNER SITES

BREATH, CPC-M, TLRC, UGMLC

OVERVIEW

Diffuse parenchymal lung diseases (DPLD) comprise more than 100 different entities yet share similar pathomechanistic principles, including progressive fibrosis of the pulmonary interstitium, distortion of normal lung architecture, and respiratory failure. Fibrotic alterations in DPLD can occur secondary to acute or chronic lung injury provoked by chemotherapy, toxin inhalation, collagen vascular disease, ventilation, or as an idiopathic entity (idiopathic interstitial pneumonia).  Most DPLD patients exhibit a poor prognosis in the absence of medical treatment. One form of DPLD, Idiopathic Pulmonary Fibrosis (IPF), in particular, displays a progressive, devastating, and ultimately fatal course of disease which is largely resistant to medical treatment. As such, lung transplantation remains the only therapeutic intervention with a known survival benefit for IPF patients. Due to the urgent unmet medical need, the DZL DPLD program primarily focuses on IPF.  The DZL aims to identify novel molecular paradigms and targets for the treatment of IPF, with the expectation that such discoveries will be transferable to positive outcomes for patients with other forms of DPLD.

MAJOR RESEARCH GOALS

  • Continuous acquisition, maintenance, and provision of well-characterized patient histories and biomaterials
  • Exploration of health economics of DPLD including evaluation of different aspects of patient care and the cost-effectiveness of treatment options
  • Precise identification of initial trigger events and secondary hits in fibrosis
  • Careful dissection of early cellular responses during the development of fibrosis (e.g., regenerative responses, developmental pathways, cellular plasticity, trafficking and crosstalk, fibroblast activation, and matrix deposition)
  • Exploration of cell-based therapies for treatment of DPLD

DPLD:  Selected Publications from DZL Faculty Members Published Since 2010

Aumiller V, Balsara N, Wilhelm J, Günther A, Königshoff M. WNT/β-catenin signaling induces interleukin 1β expression by alveolar epithelial cells in pulmonary fibrosis. Am J Respir Cell Mol Biol. 2013; in press.

Behr J, Günther A, Ammenwerth W, Bittmann I, Bonnet R, Buhl R, Eickelberg O, Ewert R, Gläser S, Gottlieb J, Grohé C, Kreuter M, Kroegel C, Markart P, Neurohr C, Pfeifer M, Prasse A, Schönfeld N, Schreiber J, Sitter H, Theegarten D, Theile A, Wilke A, Wirtz H, Witt C, Worth H, Zabel P, Müller-Quernheim J, Costabel U. [German guideline for diagnosis and management of idiopathic pulmonary fibrosis].  Pneumologie. 2013; Feb;67(2):81-111. doi: 10.1055/s-0032-1326009. Epub 2013 Jan 16. German.

Fernandez IE, Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet. 2012; Aug 18;380(9842):680-8. doi: 10.1016/S0140-6736(12)61144-1.

Rock J, Königshoff M.  Endogenous lung regeneration: potential and limitations. Am J Respir Crit Care Med. 2012; Dec 15;186(12):1213-9. doi: 10.1164/rccm.201207-1151PP. Epub 2012 Sep 20.

Korfei M, Schmitt S, Ruppert C, Henneke I, Markart P, Loeh B, Mahavadi P, Wygrecka M, Klepetko W, Fink L, Bonniaud P, Preissner KT, Lochnit G, Schaefer L, Seeger W, Guenther A. Comparative Proteomic Analysis of Lung Tissue from Patients with Idiopathic Pulmonary Fibrosis (IPF) and Lung Transplant Donor Lungs. J Proteome Res. 2011; 10(5):2185-205.

Wygrecka M, Kwapiszewska G, Jablonska E, Gerlach S, Henneke I, Zakrzewicz D, Guenther A, Preissner KT, Markart P. Role of Protease-activated Receptor-2 in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2011; 183:1703-14.

Pullamsetti SS, Savai R, Dumitrascu R, Dahal BK, Wilhelm J, Konigshoff M, Zakrzewicz D, Ghofrani HA, Weissmann N, Eickelberg O, Guenther A, Leiper J, Seeger W, Grimminger F, Schermuly RT.  The role of dimethylarginine dimethylaminohydrolase in idiopathic pulmonary fibrosis. Sci Transl Med. 2011; Jun 15;3(87):87ra53. doi: 10.1126/scitranslmed.3001725.

Königshoff M, Dumitrascu R, Udalov S, Amarie OV, Reiter R, Grimminger F, Seeger W, Schermuly RT, Eickelberg O.  Increased expression of 5-hydroxytryptamine2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention.Thorax. 2010; Nov;65(11):949-55. doi: 10.1136/thx.2009.134353. Epub 2010 Jul 29.

Mahavadi P, Korfei M, Henneke I, Liebisch G, Schmitz G, Gochuico BR, Markart P, Seeger W, Ruppert C, Guenther A. Epithelial stress and apoptosis underlie Hermansky-Pudlak syndrome associated interstitial pneumonia. Am J Respir Crit Care Med. 2010; 182(2):  207-219.